Three areas of research on hormonal control of adipocyte metabolism are summarized: (A) Previously, we reported the discovery of perilipin, an adipocyte-specific protein that is associated with the lipid storage droplet and multiply phosphorylated upon elevation of cAMP. From an adipocyte expression library we have obtained cDNA that contains the entire predicted coding sequence for perilipin. Immunocytochemistry at the electron microscope level shows that the protein is associated intimately with the lipid surface in storage droplets. However, studies in biotin-deficient cells, in which lipid accumulation but not perilipin synthesis is depressed indicate that perilipin production is related to lipid surface area, rather than lipid mass. (B) Extending our finding that insulin rapidly activates a phospholipase activity and protein kinase C activity in adipocytes, we have found that adipocytes contain at least five of the known protein kinase C isozymes. Moreover, plasma membranes of cells stimulated with insulin, vasopressin, and phorbol ester reveal different enzyme profiles upon FPLC chromatography, indicating that these agents stimulate different protein kinase C isozymes. (C) Previously, we found that Interleukin-6 (IL-6) acts directly on adipocytes to inhibit lipoprotein lipase activity, data that suggest a role for this cytokine in cachexia. Also, endogenous IL-6 production by precursor 3T3-Ll fibroblasts was strongly inhibited by dexamethasone, an agent which stimulates the cells to differentiate into adipocytes. We now find that addition of exogenous IL-6 together with dexamethasone inhibits differentiation. Moreover, at all stages during the differentiation process, tumor necrosis factor stimulates IL-6 production. Taken together, these observations strongly suggest a pathophysiological autocrine role for IL-6 in adipocyte metabolism and as a mediator of other cytokines.